The invention relates to a unit-dose discharging device of the type in which a single cylinder containing one dose of a flowable substance to be discharged is moved manually relative to a piston in order to expel the contents of the cylinder through a nozzle opening in the piston. This device is particularly adapted for intranasal adminstration of a predetermined dose of a pharmaceutical substance in liquid form. The device is suited for the intranasal administration of the drug sumatriptan for use in the treatment of conditions associated with cephalic pain, such as cluster headache, chronic paroxysmal hemicrania, headache associated with vascular disorders, headache associated with substances or their withdrawal, tension headache, and in particular migraine.
U.S. Pat. No. 4946069--equivalent to European Patent Publication No. 0311863--describes this type of device. The device has a hollow casing with a nozzle extending from one end, the other end of the casing being open. A piston extends towards the body of the casing from the nozzle and a cylinder containing a dose of the substance to be discharged is mounted on the piston. The piston has at least one discharge channel along its length communicating with the nozzle outlet. On both sides of the nozzle, the casing has rounded shoulders on which two fingers of the user's hand can rest. The device is thus generally oval in plan view. Two opposite sides of the casing have recesses so that the thumb of the user's hand can extend across the shorter dimension of the casing, in contact with the cylinder.
Thus, to use the device, the user simply holds it in one hand with the nozzle at one nasal cavity and presses the container with his or her thumb. Since the volume of the container is known, since the container is filled with a predetermined amount of the substance, and since the pump stroke of the cylinder is defined by the device, a unit dose of the pharmaceutical substance can be reliably and easily administered. The device is disposable after use.
Although the device is relatively simply constructed and is easy to use, a disadvantage does arise from the simple construction. The disadvantage is that, since the discharge channel or channels through the piston communicate with the outside environment, the contents of the cylinder are not entirely closed off from the outside. There is therefore a possibility of loss of the contents of the cylinder over time through evaporation. There is also the problem of contamination, for example microbiological contamination, which is a particular disadvantage where pharmaceuticals are being dispensed. Thus, the device would also require hermetically sealed packaging, e.g. double foil blister packaging, which can make the pack large and cumbersome for the user to carry.
A solution to the problem of the open cylinder of the known device has been briefly mentioned by the proprietors of the above mentioned U.S. Pat. No. 4946069, namely Ing. Erich Pfeiffer GmbH & Co. KG, in U.S. Pat. No. 4921142--equivalent to European Patent Publication No. 218840. In these publications there is mentioned the possibility of the discharge channel being sealed by a membrane which is broken by the pressure inside the container when it is pushed onto the piston. In the equivalent German publication, DE-OS-3631341, there is also described the possibility of the membrane being broken by a penetrating element fitted in the container. However, since the seal is formed on the piston of the discharging device there remains the disadvantage that the container which holds the substance to be discharged can remain unsealed for a period of time before it is fitted onto the device. The potential for contamination of the contents of the container thus still remains.
Pfeiffer propose another solution in European Patent Publication No. 0388651. In this publication there is disclosed a device in which the cylinder has a central pin extending from its base along the central axis, the pin having a diameter slightly less than that of the central discharge channel of the piston. The pin, however, has a hollow flared end which, at least in theory, seals against the mouth of the discharge opening of the piston. Upon actuation by the user, the pin is forced into the discharge channel and the flared end is deformed inwardly, thereby allowing the contents of the cylinder to flow along the channel and out through the nozzle. In practice, it may be difficult to achieve a reliable seal with this arrangement, and the problem with respect to evaporation around the piston flanges is not wholly overcome. Again the container is not sealed for a time before it is fitted onto the discharge device.
In European Patent Publication No. 452728 (Coster) there is described similar type of discharge device which, like the above mentioned Pfeiffer proposal, has a membrane seal. The membrane is fitted immediately behind the nozzle opening and has a pre-formed slit which opens under a predetermined pressure.
A slightly different form of the device is described in European Patent Publication No. 407276 --(Valois) equivalent to Canadian Patent No. 2020425. In this device, the substance to be discharged is contained within the body of the device and is expelled by the user pressing a piston into the device. The substance, typically a powder, may be sealed off from the piston by means of a tearable partition and the piston can be formed with a penetrating member. Movement of the piston firstly increases pressure behind the partition and then the partition is broken by the penetrating member, the compressed air expelling the powder.
In a different art, syringes are known which have a membrane sealing the syringe barrel and a double ended discharge needle. In use, pressure on the plunger of the syringe moves the membrane towards the rear end of the needle, which then punctures the membrane, and further movement of the plunger discharges the contents
U.S. Pat. No. 4017007 (Ciba-Geigy) describes a dispenser which includes a single dose container having a compressed air inlet opening and a closable discharge orifice. The container can either be mounted on a piston pump separately or the container and the pump can be combined in an integral container pump assembly. The valve means includes a breakable diaphragm which is located at the junction of the inlet opening of the container and the compressed air outlet of the pump. A pin is mounted on the forward face of the piston of the pump. During compression, when the front face of the piston reaches the end of its stroke, the diaphragm is ruptured by the pin and the compressed air surges into the interior of the container to thereby expel the product out through the discharge orifice.
International Patent Publications Nos. WO91/12197 and WO91/12198 (CP Packaging) describe unit dose assemblies consisting of compressible tubes, sealed by a thin wall, and closed by caps. In both cases, the cap has an inner spike and when the cap is pushed onto the tube the thin wall is punctured to allow the contents to be dispersed. In the first case, the contents are dispersed through the spike, which is hollow, onto an applicator pad on the cap. In the second case, the cap is removed to allow the contents of the tube to be expelled.
European Patent Publication No. 282338 (Unidec) discloses a liquid dispenser comprising a compressible container and an applicator with an internal spike. When the container is compressed, a membrane which seals the container is forced onto the spike by means of the pressure inside the container. The contents are then expelled through the applicator.